Clinical And Network Pharmacological Study On Modified Zhenwu Decoction In Treating Chronic Heart Failure (Yang Deficiency And Flooding Syndrome)

Objective: To observe the clinical effect of Modified Zhenwu Decoction on patients with chronic heart failure.Methods: Sixty patients from the outpatient department and ward of the Department of Cardiology,Affiliated Hospital of Shandong University of Traditional Chinese Medicine were collected and randomly divided into treatment group and control group,with 30 cases in both groups.The control group was treated with standard western medicine for chronic heart failure,while the treatment group was treated with Modified Zhenwu Decoction plus standard western medicine for 4 weeks.The left ventricular ejection fraction(LVEF),6-minute walking distance,serum N-terminal B-type natriuretic peptide(NT-pro BNP),uric acid and TCM symptom score were compared between the two groups before and after treatment,and the clinical efficacy and safety were evaluated.Results: There is no significant difference in general situation between the two groups(P > 0.05),which is comparable.After 4 weeks of treatment,(1)Comparison of TCM syndromes: The scores of TCM syndromes such as palpitation,shortness of breath,cough,frothy sputum and chills in the treatment group were lower than those in the control group,with statistical significance(P < 0.05).(2)Cardiac ultrasound examination: LVEF was improved before and after treatment,and the difference was statistically significant.The LVEF level in the treatment group was significantly higher than that in the control group(P < 0.05).(3)Laboratory indicators: NT-pro BNP and uric acid in both groups were lower than those before and after treatment,and the difference was statistically significant(P < 0.05).Conclusion: The modified Modified Zhenwu Decoction can effectively improve the cardiac function and clinical symptoms of CHF patients,improve the LVEF of patients,and improve the quality of life of patients,without adverse reactions.Objective: To explore the mechanism of Modified Zhenwu Decoction in treating chronic heart failure by means of network pharmacology.Methods: The active ingredients of all drugs in Modified Zhenwu Decoction were retrieved by TCMSP database,and the target points corresponding to the active ingredients of drugs were predicted by TCMSP and Swiss Target Prediction.Search the disease targets of chronic heart failure in Gene Cards,OMIM and Dis Ge NET databases.The network diagram of "drug-component-target-disease" was constructed by using Cytoscape3.7.2software.Then,based on STRING database,the network diagram of protein interaction(PPI)was constructed,and the core targets of Modified Zhenwu Decoction in treating chronic heart failure were screened by using Cytoscape3.7.2 software.Using DAVID database,the analysis of gene ontology(GO)and the analysis of gene encyclopedia(KEGG)pathway enrichment were realized.Autodock software was used to dock the main active components and core targets in Modified Zhenwu Decoction.Results: 198 effective active ingredients of Modified Zhenwu Decoction were screened,155 potential targets and 9547 targets of chronic heart failure were predicted,and Venn diagram showed 151 mapping targets of drugs and diseases.The values of IL6,VEGFA,TNF,TP53,EGF,MAPK1,JUN,PTGS2 and other targets are higher,which may be the key targets of Modified Zhenwu Decoction in treating chronic heart failure.GO enrichment analysis found that,Active components and targets are mainly involved in response to drug,positive regulation of cell proliferation,response to hypoxia,Biological processes such as positive regulation of nitric oxide biosynthetic process,postsynaptic membrane,integral component of plasma membrane,enzyme binding,drug binding,etc.KEGG enrichment analysis found that,Target genes are mainly concentrated in neuroactive ligand-receptor interaction,Calcium signaling pathway,TNF signaling pathway,In c GMP-PKG signaling pathway and HIF-1 signaling pathway,it is suggested that Modified Zhenwu Decoction may participate in the treatment of chronic heart failure through these signaling pathways.The results of molecular docking showed that the main active components in Modified Zhenwu Decoction had lower binding energy with CCL2,MPO,TNF,TP53,VEGFA and other targets,and had better docking ability.Conclusion: The treatment of chronic heart failure with modified Modified Zhenwu Decoction has the characteristics of multi-component,multi-target and multi-pathway,and its mechanism may be related to key targets such as IL6,VEGFA,TNF,TP53,EGF,MAPK1,JUN and PTGS2,as well as signal pathways such as calcium signal pathway,TNF signal pathway and HIF-1 signal pathway.